The endoplasmic reticulum acetyltransferases ATase1/NAT8B and ATase2/NAT8 are differentially regulated to adjust engagement of the secretory pathway

AbstractN ε‐lysine acetylation of nascent glycoproteins within the endoplasmic reticulum (ER) lumen regulates the efficiency of the secretory pathway. The ER acetylation machinery consists of the membrane transporter, acetyl‐CoA transporter 1 (AT‐1/SLC33A1), and two acetyltransferases, ATase1/NAT8B and ATase2/NAT8. Dysfunctional ER acetylation is associated with severe neurological diseases with duplication ofAT ‐1/SLC33A1 being associated with autism spectrum disorder, intellectual disability, and dysmorphism. Neuron ‐specific AT‐1 overexpression in the mouse alters neuron morphology and function, causing an autism‐like phenotype, indicating that ER acetylation plays a key role in neurophysiology. As such, characterizing the molecular mechanisms that regulate the acetylation machinery could reveal critical information about its biology. By using structure‐biochemistry approaches, we discovered that ATase1 and ATase2 share enzymatic properties but differ in that ATase1 is post‐translationally regulated via acetylation. Furthermore, gene expression studies revealed that the promoters ofAT ‐1,ATase1, andATase2 contain functional binding sites for the neuron ‐related transcription factors cAMP response element‐binding protein (CREB) and the immediate early genes c‐FOS and c‐JUN, and thatATase1 andATase2 exhibit additional modes of transcriptional regulation relevant to aging and Alzheimer's disease. In vivo rodent gene expression experiments r...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research

Related Links:

Contributors : Yanina I Pachimal ; Adva Hadar ; Iris Grigg ; Vlasta Korenkova ; Oxana Kapitansky ; Gidon Karmon ; Michael Gershovits ; Laura C Sayas ; Frank R Kooy ; Johannes Attems ; David Gurwitz ; Illana GozesSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDe novo mutated ADNP is a most prevalent gene driving syndromic autism with intellectual disability. Using droplet digital PCR and RNA sequencing we identified somatic mutations in ADNP and in other genes in the olfactory bulb and hipocampi of Alzheimer's disease (AD) patients.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
Molecular Psychiatry, Published online: 30 October 2019; doi:10.1038/s41380-019-0563-5Discovery of autism/intellectual disability somatic mutations in Alzheimer's brains: mutated ADNP cytoskeletal impairments and repair as a case study
Source: Molecular Psychiatry - Category: Psychiatry Authors: Source Type: research
ánchez As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmac...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Albert Sanfeliu1, Karsten Hokamp2, Michael Gill1 and Daniela Tropea1,3*1Neuropsychiatric Genetics, Department of Psychiatry, School of Medicine, Trinity Translational Medicine Institute, St James Hospital, Dublin, Ireland2Department of Genetics, School of Genetics and Microbiology, Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland3Department of Psychiatry, School of Medicine, Trinity College Institute for Neuroscience, Trinity College Dublin, Dublin, IrelandRett syndrome is a rare neuropsychiatric disorder with a wide symptomatology including impaired communication and movement, cardio-respiratory abno...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Conclusion The key problem with the ND field is the lack of understanding in the events preceding the development of protein-based markers – such as Tau – currently used to diagnose NDs. By this stage, the diseases become more difficult to treat. SncRNAs play an important regulatory role in the maintenance of the homeostatic brain. Therefore, changes in their concentration levels can be indicative of mechanistic changes that could precede protein-based markers. One single sncRNA biomarker is unlikely to differentiate between diseases. However, a combination of sncRNA biomarkers could be illustrative of the me...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Abstract Over the past 20 years the structure and function of Reelin, an extracellular glycoprotein with a role in cell migration and positioning during development has been elucidated. Originally discovered in mice exhibiting a peculiar gait and hypoplastic cerebellar tissue, Reelin is secreted from Cajal-Retzius neurons during embryonic life and has been shown to act as a stop signal, guiding migrating radial neurons in a gradient-dependent manner. Reelin carries out its function by binding to the receptors, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) resulting in the p...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
Discussion We have found that, in the human genome, the promoter regions of ID-associated genes are uniquely enriched in MER41 LTRs. More specifically, nine ID-associated genes that are putatively important in cognitive evolution exhibit MER41 LTRs in their promoter regions. As more than 100 families of HERV are integrated into our genome, it was important to determine whether our findings are specific to MER41 and to ID-associated genes, and if so to what extent. Among the 133 families of HERV explored here, MER41 is the only family whose LTRs were found with statistically high frequency in the promoter regions of ID-ass...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions: These findings support the notion that MS patients exhibit an altered multisensory perception in the SiFi task and that their susceptibility to the perceptual illusion is negatively correlated with their neuropsychological test performance. Since MS lesions affect white matter tracts and cortical regions which seem to be involved in the transfer and processing of both crossmodal and cognitive information, this might be one possible explanation for our findings. SiFi might be considered as a brief, non-expensive, language- and education-independent screening test for cognitive deficits in MS patients. Intr...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Novel Contribution of Secreted Amyloid-β Precursor Protein to White Matter Brain Enlargement in Autism Spectrum Disorder Deborah K. Sokol1, Bryan Maloney2, Cara J. Westmark3 and Debomoy K. Lahiri2,4* 1Pediatrics Section, Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States2Indiana Alzheimers Disease Center, Department of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States3Department of Neurology, University of Wisconsin, Madison, WI, United States4Department of Medical and Molecular Genetics, Indiana Un...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research
Abstract Autism is a wide spread neurodevelopmental disorder with growing morbidity rates, affecting more boys than girls worldwide. Activity-dependent neuroprotective protein (ADNP) was recently recognized as a leading gene accounted for 0.17% of autism spectrum disorder (ASD) cases globally. Respectively, mutations in the human ADNP gene (ADNP syndrome), cause multi-system body dysfunctions with apparent ASD-related traits, commencing as early as childhood. The Adnp haploinsufficient (Adnp+/-) mouse model was researched before in relations to Alzheimer's disease and autism. Adnp+/- mice suffer from deficient soc...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
More News: Alzheimer's | Autism | Biochemistry | Biology | Brain | Disability | Genetics | Molecular Biology | Neurology | Neuroscience | Study